Efeitos do estradiol e dos canais TRPV1 sobre a termorregulação em ratas

Abstract

Menopause is characterized by a transition period in a woman's life when occurs menses interruption for 12 months after the end of the menstrual period. At this stage, there is a commitment in ovarian hormones secretion, including estradiol’s secretion (E2). Considering the common reported disorders, there are vasomotor, sleep–wake cycle and thermoregulation changes. Heat waves, also known as hot flushes, are considered the main clinical manifestation of discomfort, affecting approximately 75% of middle-aged women. It is known that this symptom can be minimized by hormone replacement therapy although the mechanism for this is not well elucidated. In addition, many studies show Transient Receptor Potential Channel-Vanilloid 1(TRPV1) as an important component in thermoregulatory control. Therefore, we hypothesized that this channel as well as E2 may be involved in the circadian and homeostatic control of temperature in female rats. We evaluated in ovariectomized adult female rats (OVX) E2’s effects on the circadian rhythms in body core temperature variations (Tcore) and spontaneous locomotor activity (ALE) for 4 days. To check the importance of the TRPV1 channel in association with this hormone, OVX rats treated with E2 received resiniferatoxin (RTX) agonist intraperitoneal injection (i.p.) at sufficient dose to cause desensitization of these channels in abdominal cavity. The same rhythmic parameters were analyzed again (body core temperature and ALE). The hormone’s effects on thermoregulation were evaluated during heat challenge at 34 ° C for 40 minutes, when Tcore and Tskin were measured. Based on these values, we calculated the threshold and the sensitivity to heat dissipation response. The metabolic rate was also measured under the same conditions of thermal challenge through oxygen consumption (VO2) rates. E2 treated rats desensitized by RTX were also subjected to thermal challenge and the same thermoregulatory parameters were analyzed. The duration of E2 treatment in all experimental protocol was 14 days and the control groups were represented by animals treated with E2 vehicle (corn oil) and RTX (20% ethanol in saline). The core temperature (Tcore) was obtained by implantation of a telemetric sensor in the abdominal cavity and the tail skin temperature (Tskin), used to evaluate the heat dissipation capacity, was measured by a precision thermometer. The implants containing oil or E2 were inserted subcutaneously (s.c.) in animal’s backs. Relativeuterine weight and CCK test proved the effectiveness of treatments with E2 and RTX, respectively. Some differences were observed between Tcore of E2-treated rats and oil-treated rats during dark phase, but there was no change in the amplitude rhythm. Groups of animals treated with E2 + RTX and E2 + vehicle also showed higher values of Tcore predominantly in the dark phase, so the amplitude of this rhythm was higher in animals desensitized. ALE’s amplitude did not change in the RTX-treated groups compared to respective control groups. In relation to thermal challenge, there was an increase in Tcore of oil and E2 rats. However, the heat dissipation from tail skin was most effective in this last group. Estradiol reduced the threshold of heat dissipation and increased sensitivity. In the E2 + RTX rats, the Tcore during thermal challenge was notably higher than the E2 + vehicle group, which may be related to impaired heat dissipation through tail skin. The absence of abdominal TRPV1 channel also increased the threshold for heat dissipation and reduced sensitivity in these animals compared to the control group. In conclusion, both the E2 as TRPV1 channels are important for homeostatic and circadian temperature control, whereas the lack of these components compromises thermoregulatory rats’ mechanisms. So both are classified as potential therapeutic targets that help to explain the mechanisms involved in heat waves present in menopause.